Trial Outcomes & Findings for A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA) (NCT NCT01544114)

Last Updated: 2024-12-17

Results Overview

An AE is defined as the development of an undesirable medical condition or the deterioration of a preexisting medical condition, whether or not considered causally related to treatment. An SAE is defined as an AE occurring during any study phase (ie, run-in, treatment, washout, follow-up), that fulfils one or more of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. AEs were considered treatment-emergent if they occurred after the first dose of study drug. Events were categorized as mild, moderate, and severe; participants were represented only with the maximum reported intensity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

46 participants

Primary outcome timeframe

SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.

Results posted on

2024-12-17

Participant Flow

A total of 51 participants signed informed consent; 5 participants were not assigned to treatment (eligibility criteria not fulfilled).

Participant milestones

Participant milestones
Measure	VIMOVO 250 mg/20 mg 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Overall Study STARTED	4	20	22
Overall Study COMPLETED	3	16	17
Overall Study NOT COMPLETED	1	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	VIMOVO 250 mg/20 mg 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Overall Study Withdrawal by Subject	0	0	3
Overall Study Lost to Follow-up	0	2	0
Overall Study Adverse Event	1	1	2
Overall Study Protocol Violation	0	1	0

Baseline Characteristics

A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=20 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=22 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=46 Participants Total of all reporting groups
Age, Continuous	12.8 years STANDARD_DEVIATION 0.96 • n=5 Participants	13.6 years STANDARD_DEVIATION 1.47 • n=7 Participants	13.8 years STANDARD_DEVIATION 1.33 • n=5 Participants	13.6 years STANDARD_DEVIATION 1.37 • n=4 Participants
Age, Customized Age Group · 12 years old	2 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Age, Customized Age Group · 13 years old	1 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Age, Customized Age Group · 14 years old	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Age, Customized Age Group · 15 years old	0 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Age, Customized Age Group · 16 years old	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants

PRIMARY outcome

Timeframe: SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.

Population: Safety analysis set: all participants who received at least 1 dose of study drug; participants were categorized according to the treatment medication they actually took.

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=20 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=22 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=46 Participants 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any TEAE	4 participants	16 participants	17 participants	37 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Mild TEAE	1 participants	9 participants	8 participants	18 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Moderate TEAE	3 participants	6 participants	9 participants	18 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Severe TEAE	0 participants	1 participants	0 participants	1 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any related TEAE	1 participants	6 participants	4 participants	11 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any SAE	0 participants	1 participants	0 participants	1 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any related SAE	0 participants	1 participants	0 participants	1 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any TEAE leading to death	0 participants	0 participants	0 participants	0 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any TEAE leading to DC of study drug	1 participants	1 participants	2 participants	4 participants
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug Any related TEAE leading to DC of study drug	1 participants	1 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: pre-dose, and up to 3 hours post-dose

Population: PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=16 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=20 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=40 Participants 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Pharmacokinetics (PK) of Esomeprazole: Area Under the Concentration-Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-t])	2.2 hr*µmol/L Geometric Coefficient of Variation 92	1.3 hr*µmol/L Geometric Coefficient of Variation 170	1.2 hr*µmol/L Geometric Coefficient of Variation 150	1.3 hr*µmol/L Geometric Coefficient of Variation 150

SECONDARY outcome

Timeframe: pre-dose, and up to 3 hours post-dose

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=16 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=20 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=40 Participants 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
PK of Esomeprazole: Oral Plasma Clearance (CL/F)	27 L/h Geometric Coefficient of Variation 92	44 L/h Geometric Coefficient of Variation 170	47 L/h Geometric Coefficient of Variation 150	43 L/h Geometric Coefficient of Variation 150

SECONDARY outcome

Timeframe: pre-dose, and up to 3 hours post-dose

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=16 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=20 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=40 Participants 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
PK of Esomeprazole: Absorption Rate Constant (Ka)	2.8 h^-1 Geometric Coefficient of Variation 140	2.6 h^-1 Geometric Coefficient of Variation 83	4.1 h^-1 Geometric Coefficient of Variation 70	3.3 h^-1 Geometric Coefficient of Variation 84

SECONDARY outcome

Timeframe: pre-dose, and up to 3 hours post-dose

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=16 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=20 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=40 Participants 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
PK of Esomeprazole: Oral Volume of Distribution (V/F)	28 L Geometric Coefficient of Variation 240	61 L Geometric Coefficient of Variation 120	57 L Geometric Coefficient of Variation 130	55 L Geometric Coefficient of Variation 130

SECONDARY outcome

Timeframe: Month 1 and Month 3: pre-dose, and up to 3 hours post-dose

Trough concentration was defined as lowest plasma concentration from pre-dose to 3 hours post-dose, for each individual participant.

Outcome measures

Outcome measures
Measure	VIMOVO 250 mg/20 mg n=4 Participants 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=17 Participants 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=20 Participants 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
PK of Naproxen: Trough Plasma Concentrations Month 1	63.09 µg/mL Geometric Coefficient of Variation 40.1	19.29 µg/mL Geometric Coefficient of Variation 1334.9	40.71 µg/mL Geometric Coefficient of Variation 277.3	—
PK of Naproxen: Trough Plasma Concentrations Month 3	63.16 µg/mL Geometric Coefficient of Variation 67.3	33.91 µg/mL Geometric Coefficient of Variation 476.0	40.69 µg/mL Geometric Coefficient of Variation 325.4	—

Adverse Events

VIMOVO 250 mg/20 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

VIMOVO 375 mg/20 mg

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

VIMOVO 500 mg/20 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Total

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VIMOVO 250 mg/20 mg n=4 participants at risk 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 375 mg/20 mg n=20 participants at risk 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	VIMOVO 500 mg/20 mg n=22 participants at risk 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total n=46 participants at risk 250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Hepatobiliary disorders Hepatitis Acute	0.00% 0/4 • SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.	5.0% 1/20 • SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.	0.00% 0/22 • SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.	2.2% 1/46 • SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.

Other adverse events

Additional Information

Julie Ball, Executive Director of Clinical Development & Operations

Horizon Pharma, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
Publication restrictions are in place

Restriction type: OTHER